Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020505 (hyperphagia)
 6,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our previous studies have shown that stimulation of mu-opioid receptors within the nucleus accumbens preferentially enhances intake of palatable food containing sucrose and fat; thus, opioids in this brain area may mediate the rewarding characteristics of food by modulating taste and macronutrient preference. The present study was designed to further explore the nature of the involvement of striatal opioids in feeding behavior, such as the location of sensitive subregions of the ventral striatum and the brain neural circuits involved in opioid-mediated hyperphagia. In Experiment 1, we conducted a microinfusion mapping study of feeding behavior by microinfusion of the mu receptor agonist, D-Ala(2),NMe-Phe(4), Glyol(5)-enkephalin (0, 0.025 and 0.25 microg/0.5 microl per side; equivalent to 0, 0.04 and 0.40 nmol/0.5 microl per side), into several striatal subregions. In Experiment 2, detection of the expression of the immediate early gene, c-fos, was used to examine brain areas activated following intra-striatal microinfusion of D-Ala(2), NMe-Phe(4),Glyol(5)-enkephalin. The microinjection mapping study demonstrated a broad anatomical gradient within the striatum, with sensitivity highest in relatively more lateral and ventral regions of the striatum (ventrolateral striatum, lateral shell and core). The Fos mapping study demonstrated that circuitry including hypothalamic areas, the ventral tegmental area, the substantia nigra and the nucleus of the solitary tract was recruited by stimulation of mu receptors within the nucleus accumbens. A similar pattern was observed following stimulation of mu receptors in the dorsal striatum; however, the extent of activation was much smaller in magnitude. These results suggest that the role of mu receptors within the striatum in palatable feeding primarily involves ventral and lateral regions. Moreover, the pattern of activation in hypothalamic, midbrain and gustatory-visceral relay areas suggests that striatal mu receptors may participate in integrating motivational, metabolic and autonomic aspects of ingestive behavior.
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PMID:Enhanced intake of high-fat food following striatal mu-opioid stimulation: microinjection mapping and fos expression. 1093 32

Mu (mu) opioid agonists preferentially increase the intake of highly palatable food. Here we investigated changes in mu opioid binding in feeding- and reward-related brain regions in rats given a palatable diet for 17 weeks. Diet feeding induced variable obesity, and rats were stratified into 'high-weight gain' (HWG: weight increase, 513-695 g; n=12) and 'low-weight gain' (LWG: range: 396-502 g; n=11) groups. Chow-fed controls (n=9) gained 324-487 g during this time. Body fat mass and plasma leptin and insulin were significantly higher in LWG than in controls and even higher in HWG. mu-Receptor binding (measured in brain slices using [3H]-DAMGO (D-Ala(2), N-Me-Phe(4),Gly-ol(5)) and quantitative autoradiography) was significantly increased in specific forebrain regions of diet-fed rats. In the fundus striati, dorsal endopiriform nucleus and medial preoptic area (MPA), binding was similarly increased (30-40%; P<0.05 vs. controls) in the HWG and LWG groups. Increases in mu binding paralleled weight gain in the basolateral amygdala and basomedial amygdala, being approximately 20% above controls (P<0.001) in LWG and approximately 30% higher in HWG (P<0.05 vs. LWG). The medial habenula showed significantly higher binding (by approximately 40%) in HWG, with no significant changes in LWG. In all these areas (except the MPA), binding was significantly correlated with plasma leptin and insulin. We suggest that increased mu binding reflects decreased release of endogenous mu opioid peptides. This orexigenic system therefore seems unlikely to drive appetite for palatable food. Indeed, the mu opioid system in reward-related areas may be inhibited in dietary obesity, probably by increased plasma leptin and insulin, and this may represent a failed homeostatic attempt to limit overeating and eventually obesity.
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PMID:Diet-induced obesity increases mu opioid receptor binding in specific regions of the rat brain. 1238 55

The nucleus tractus solitarius (NTS) receives dense terminations from cranial visceral afferents, including those from the gastrointestinal (GI) system. Although the NTS integrates peripheral satiety signals and relays this signal to central feeding centers, little is known about which NTS neurons are involved or what mechanisms are responsible. Proopiomelanocortin (POMC) neurons are good candidates for GI integration, because disruption of the POMC gene leads to severe obesity and hyperphagia. Here, we used POMC-enhanced green fluorescent protein (EGFP) transgenic mice to identify NTS POMC neurons. Intraperitoneal administration of cholecystokinin (CCK) induced c-fos gene expression in NTS POMC-EGFP neurons, suggesting that they are activated by afferents stimulated by the satiety hormone. We tested the synaptic relationship of these neurons to visceral afferents and their modulation by CCK and opioids using patch recordings in horizontal brain slices. Electrical activation of the solitary tract (ST) evoked EPSCs in NTS POMC-EGFP neurons. The invariant latencies, low failure rates, and substantial paired-pulse depression of the ST-evoked EPSCs indicate that NTS POMC-EGFP neurons are second-order neurons directly contacted by afferent terminals. The EPSCs were blocked by the glutamate antagonist 2,3-dihydroxy-6-nitro-7-sulfonyl-benzo[f]quinoxaline. CCK increased the amplitude of the ST-stimulated EPSCs and the frequency of miniature EPSCs, effects attenuated by the CCK1 receptor antagonist lorglumide. In contrast, the orexigenic opioid agonists [D-Ala(2), N-Me-Phe(4), Gly-ol(5)]-enkephalin and met-enkephalin inhibited both ST-stimulated EPSCs and the frequency of miniature EPSCs. These findings identify a potential satiety pathway in which visceral afferents directly activate NTS POMC-EGFP neurons with excitatory inputs that are appropriately modulated by appetite regulators.
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PMID:Proopiomelanocortin neurons in nucleus tractus solitarius are activated by visceral afferents: regulation by cholecystokinin and opioids. 1581 88

The experimental question is whether hypothalamic opioids, known to stimulate consummatory behavior, control a link to the nucleus accumbens (NAc). It was hypothesized that opioids injected in the hypothalamic paraventricular nucleus (PVN) alter the balance of dopamine (DA) and acetylcholine (ACh) in the NAc in a manner that fosters appetite for food or ethanol. Rats were implanted with two guide shafts, one in the NAc to measure extracellular DA and ACh by microdialysis and the other in the PVN for microinjection of opioid mu- and delta-agonists, an antagonist, or saline vehicle. The compounds tested were morphine, the mu-receptor agonist [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-Enkephalin (DAMGO), the delta-receptor agonist D-Ala-Gly-Phe-Met-NH2 (DALA), and the opioid antagonist naloxone methiodide (m-naloxone). Morphine in the PVN increased the release of accumbens DA (+41%) and decreased ACh (-35%). Consistent with this, the opioid antagonist m-naloxone decreased DA (-24%) and increased ACh (+19%). In terms of receptor involvement, DAMGO dose-dependently increased DA to up to 209% of baseline. Simultaneously, ACh levels were markedly decreased to 55% of baseline. The agonist DALA produced a smaller but significant, 34% increase in DA, without affecting ACh. In contrast, control injections of saline had no significant effect. These results demonstrate that mu- and delta-opioids in the PVN contribute to the control of accumbens DA and ACh release and suggest that this circuit from the PVN to the NAc may be one of the mechanisms underlying opiate-induced ingestive behavior as well as naltrexone therapy for overeating and alcoholism.
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PMID:Opioids in the hypothalamus control dopamine and acetylcholine levels in the nucleus accumbens. 1994 54